P2a Open Label Study to Evaluate 2-HPβCD in Subjects With Diabetic Kidney Disease

Today's cyclodextrin, ,

Today’s cyclodextrin: After a long time, HPBCD will be evaluated again in clinics, now in a new application.
ZyVersa Therapeutics Inc. is sponsoring this Phase 2a open-label, two- to three-center study to evaluate the clinical efficacy and safety of one dose level of 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) given intravenously in adult patients with type 2 diabetes, diabetic kidney disease (DKD), and proteinuria.

According to the proposed mechanism of action, HPBCD entraps and passively removes intracellular cholesterol from the kidney. It is also believed to promote active cholesterol removal through up-regulation of cholesterol efflux transporters ABCA1 and ABCG1.

Study Details | P2a Open Label Study to Evaluate 2-HPβCD in Subjects With Diabetic Kidney Disease | ClinicalTrials.gov


Methods for the treatment of chronic kidney disease

drug development, , ,

We are happy to announce the acceptance of a great patent from CarboHyde’s collaborator, Renatus, a pharmaceutical company focused on developing cyclodextrin-based cholesterol metabolism modulators. Renatus is a pharmaceutical company whose mission is to provide safe and effective treatment options for the treatment of numerous cholesterol-driven diseases such as chronic kidney disease, atherosclerosis, and Alzheimer’s diseases. The core technology of the company allows the normalization of cholesterol homeostasis by removal of excessive and toxic cholesterol within diseased cells without significant harmful effects on normal cells.

The lead asset RN-005 is a cholesterol metabolism modulator that has proven strong therapeutic efficacy in preclinical models of both diabetic kidney disease (DKD) and focal segmental glomerulosclerosis (FSGS) wherein dysregulated cholesterol metabolism causes progressive damage and loss of function in the kidney. The gamma-cyclodextrin oligomers are effective in cholesterol metabolism enhancement, cholesterol efflux, reducing inflammatory cytokine secretion, renal clearance of cholesterol, and/or reducing albuminuria. Therefore, the gamma-cyclodextrin oligomers can be used to treat or alleviate chronic kidney disease, symptoms thereof and/or complications related to chronic kidney disease.

Espacenet – METHODS FOR THE TREATMENT OF CHRONIC KIDNEY DISEASE

New cyclodextrin dimer patent!

Today's cyclodextrin,

today’s cyclodextrin:
I am proud to share this new patent from Cyclarity Therapeutics not only because of the fantastic chemistry and excellent drug development but also as CarboHyde CSO Milo Malanga is among the inventors!

Cyclodextrin dimers are used to target 7-ketocholesterol, eventually to reverse atherosclerotic plaques.
Check out for more info: Espacenet – US2024043661A1

Congratulation to Milo and the geat team at Cyclarity!

Oral alpha-cyclodextrin reverses cholesterol-crystal-induced retinal pathology in a rodent model of type 2 diabetes

Today's cyclodextrin, ,

Today’s cyclodextrin a study showing how alpha-CD treatment could be used in type-2 diabetes patients.
Cholesterol crystals were eliminated from the retinas of diabetic mice after oral alpha-cyclodextrin treatment. These findings demonstrate that T2D is associated with cholesterol crystal-induced retinal pathology that is improved using oral alpha-cyclodextrin. Improvements were observed in inflammation, neural function and visual response.

Oral alpha-cyclodextrin reverses cholesterol-crystal-induced retinal pathology in a rodent model of type 2 diabetes (T2D). | IOVS | ARVO Journals

Cyclodextrin-loaded nanobubbles reduce cholesterol and atherosclerosis in vivo

drug delivery, ,

While the uses of cyclodextrin as active ingredients is emerging both by the number of target diseases, companies developing them and types of CDs used, their efficient delivery remains a challenge.
The nanobubbles presented here could incorporate the CDs, accumulate in the atherosclerotic lesions, the release of CD and the reduce the total plaque area in the entire aorta and eventually reduce cholesterol level in mice plasma.
Cyclodextrin-loaded nanobubbles reduce cholesterol and atherosclerosis in vivo | European Heart Journal | Oxford Academic (oup.com)

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

drug delivery, Today's cyclodextrin,

Today’s cyclodextrin is a smart and very practical study, highlighting how different cyclodextrins added to a liposomal formulation could influence the release of the active load.

The results demonstrated that the CDs effect on the membrane depends on the CD type, CD concentration, and membrane cholesterol content. The investigated CDs exhibited an instantaneous permeabilizing effect promoting vesicle leakage of API from the various membranes; this effect increased with CDs concentration. Among the studied CDs, α-CD, β-CD, and RAMEB were the most permeabilizing CDs on the different membranes.

Ghenwa Nasr, Helene Greige, Sophie Fourmentin, Abdelhamid ELAISSARI, Nathalie Khreich

BJOC – Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration (beilstein-journals.org)

Treatment of hypertriglyceridemia with 2-hydroxypropyl-beta-cyclodextrin

drug development, drug discovery,

Fascinating therapeutic application of cyclodextrins have been published by Beren Therapeutics. Earlier the company already patented the use in the therapy of familial hypercholesterolemia, now they propose using hydroxypropyl-BCD against hypertriglyceridemia.
In the 2nd patent composition and purification is reported of a compounds that has a surprisingly high DS (DS-10 being the main component), which composition is far from the materials used as excipients.

WO2023156970 TREATMENT OF HYPERTRIGLYCERIDEMIA WITH 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN (wipo.int)

US20230265219 COMPOSITIONS OF HYDROXYPROPYL-BETA-CYCLODEXTRIN AND METHODS OF PURIFYING THE SAME (wipo.int)

High-Cholesterol Diet in Combination With Hydroxypropyl-β-Cyclodextrin Induces NASH-Like Disorders in the Liver of Rats

carbohydrates, ,

We are hearing a lot about how the cholesterol complexation ability of certain cyclodextrins, especially hydroxypropyl-beta-CD can be used to treat various diseases, like Alzheimer’s, Niemann Pick type C, atherosclerosis, familial hypercholesterolemia and many more.
But can this be a double-edged sword? This fascinating research suggests that High-Cholesterol Diet in Combination With Hydroxypropylβ-Cyclodextrin Induces NASH-Like Disorders in the Liver of Rats

You can read the full article here!

Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial

carbohydrates, drug development, ,

Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial.
Niemann-Pick disease type C (NPC) is a rare, fatal, pan-ethnic, autosomal recessive lysosomal storage disease characterized by progressive major organ failure and neurodegeneration. Preclinical studies confirmed the critical role of systemically administered hydroxypropyl-β-cyclodextrin (HP-β-CD; Trappsol® Cyclo™) in cholesterol metabolism and homeostasis in peripheral tissues of the body, including the liver, and in the central nervous system (CNS). Herein, the pharmacokinetics (PK), safety, and efficacy of HP-β-CD and biomarkers of NPC were assessed in pediatric and adult patients with NPC1.
Cyclo Therapeutics, Inc. –  Caroline Hastings, Sharon Hrynkow et al

Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial – ScienceDirect

2-Hydroxypropyl-β-cyclodextrin (HPβCD) as a Potential Therapeutic Agent for Breast Cancer

Today's cyclodextrin,

today’s cyclodextrin:
Breast cancer is a global burden with the most severe subtype being triple-negative breast cancer (TNBC). Despite advances in conventional therapies, treatment for TNBC is currently lacking. Interestingly, cholesterol has gained interest as a potential therapeutic target due to cancer cells’ increased reliance on this macromolecule. Treatment with the cholesterol-depletory agent 2-hydroxypropyl-β-cyclodextrin (HPβCD) impeded the growth of cancer cells and further led to cancer cell death, which could be attributed to an altered cellular cholesterol profile following treatment. Furthermore, mice xenograft studies indicated complete eradication of early-stage tumours with no relapse, followed by a remarkable reduction in intermediate- and late-stage tumours, respectively. SFRP1 was identified as a possible molecular target facilitating the therapeutic action of HPβCD. These findings consequently potentiate cholesterol depletion as a novel anticancer strategy to be pursued.

University of the Witwatersrand – Tawanda Ziningav Reubina Wadee, Mandeep Kaur et al

See the full article here